Faridpur Med. Coll. J. 2016;11(2):74-80 Review Article Assessment of Ovarian Reserve in Infertile Patients P Begum1, DR Shaha2, L Sanjowal3, R Barua4, MK Hassan5 Abstract: Reduced ovarian reserve is a condition characterized by a reduced competence of the ovary to produce oocyte due to advanced age or congenital, medical, surgical and idiopathic causes. Age is considered to be the principal factor in determining the reduction of ovarian reserve, especially in woman over 40 years of age, but it's well known that a premature reduction of ovarian reserve can also occur in young patients. Management of patients with diminished ovarian reserve is challenging for fertility experts and frequently the only option to conceive is represented by assisted reproduction technologies. Here we review the aetiology, presentation and diagnosis of reduced ovarian reserve both in advanced and in young age and we discuss recent advances in the management of infertility of these women. Key words: Reduced Ovarian Reserve; Diminished Ovarian Reserve; Premature Ovarian Failure. Introduction: Reduced ovarian reserve is a condition of reduced women the incidence of POF is quickly increasing3. ability of the ovary to produce oocytes due to advanced Analyses performed by the Childhood Cancer Survivor age or congenital, medical, surgical and idiopathic Study show that the 6.3% of women who received cure causes. This condition, also known as Diminished for cancer suffered from acute ovarian failure. In this Ovarian Reserve (DOR) is often used to characterize manuscript we reviewed the aetiology, presentation and women at risk for poor performance with Assisted evaluation of old and young woman with reduced Reproductive Technologies (ART) due to egg factor1. ovarian reserve and we discussed recent advances in The most extreme phenotype of DOR in young age is the management of infertility of these patients. represented by Premature Ovarian Failure (POF), a disorder characterized by amenorrhea, Normal Reproductive Aging: hypoestrogenism and high gonadotropin levels in young patients under 40 years of age. Spontaneous The probable theoretical causes of decline in POF affects the 1% of women under 40 years, 0.1% of reproductive potential in women beginning at the third patients younger than 30 years and 0.01% of patients decade of life may be classified as: under the age of 20 years2. However, with the increasing of cancer cures in children and in young i. Diminished ovarian reserve 1. Dr. Poly Begum, MBBS, FCPS (Obst & Gynae), Assistant a. Quantitative decrease in oocytes Professor, Department of Obstetrics & Gynaecology, Diabetic b. Qualitative changes in oocytes Association Medical College, Faridpur. ii. Diminished uterine receptivity for implantation 2. Prof. Dr. Dipti Rani Shaha, MBBS, FCPS (Obst & Gynae), Professor & Head, Department of Obstetrics & Gynaecology, Diabetic Association Medical College, Faridpur. The diminished ovarian reserve, either by decreased quantity and/or quality of the resting follicle pool, 3. Dr. Lipika Sanjowal, MBBS, DA, MCPS (Anaesthesia), Associate Professor, Department of Anaesthesiology, Diabetic Association might decrease fertility after age 30. There is enough Medical College, Faridpur. evidence for both situations. The primordial follicle th 4. Dr. Ripon Barua, MBBS, M.Phil (Microbiology), Assistant count, which is about 20 million at the 20 week of Professor, Department of Microbiology, Faridpur Medical College, intrauterine life, starts to decrease with the process of Faridpur. apoptosis. The primordial follicles left are about 1 5. Dr. Md. Kamrul Hassan, MBBS, DCH (Pediatrics), Junior million at birth and 300 thousands at puberty. At a Consultant (Pediatrics), Faridpur Medical College Hospital, Faridpur. mean age of 37-38 years only about 25 thousands of Address of correspondence : follicles are present in the ovaries. After this age, the Dr. Poly Begum, MBBS, FCPS (Obst & Gynae), Assistant disappearance of the follicles accelerates and the curve Professor, Department of Obstetrics & Gynaecology, Diabetic Association Medical College, Faridpur. Cell: +8801913-486864, follows a biphasic pattern. The time interval between E-mail: [email protected] the beginning of 74 Assessment of Ovarian Reserve in Infertile Patients P Begum et al. accelerated follicular disappearance and menopause is subtle diminished ovarian reserve. For this reason, it constant at about thirteen years. Menstrual cycles will be reasonable to apply ovarian reserve tests become irregular about 6 years before menopause4. liberally to unexplained infertile couples. There is a time period of about 4 years between age 37 when fertility begins to decline and age 41 when The effect of diminished ovarian reserve on fertility fertility practically ends5. It is known that the age of outcome has largely been evaluated in patients treated menopause in the general populationis under 45 in 10% with ART. In this group of infertile patients the clinical of women and under 40 in 1% of women. Thus, if the entities associated with diminished ovarian reserve are time interval between the beginning of accelerated poor response to COH, increased need for exogenous follicular disappearance and menopause is constant and gonadotropin, high cancellation rates, low pregnancy about thirteen years it can be speculated that about 10% and live birth rates in ART. On the other hand, data of women in the general population will suffer from the regarding the reproductive outcome of ovulatory clinical consequences of impaired fertility in their women in a general infertility population with an thirties due to early ovarian aging. The data from ART abnormal ovarian test is insufficient. Hence, the cycles with fresh and non-donor oocytes and embryos treatment alternatives to increase the chance to have a demonstrate a decrease in embryo implantation, baby, especially in patients with an abnormal ovarian pregnancy and live birth rates per cycle when female reserve test and younger than 35 years of age, are not partner age exceeds 38. In ICSI cycles of men with yet known. obstructive azoospermia, the implantation rate decreases if the female partner age is over 37; this Ovarian Reserve Tests: finding also demonstrates the effect of age related decline in oocyte quality on reproductive performance6. Basal follicle stimulating hormone (FSH) level: Basal Data obtained from oocyte donation clearly shows that, or cycle day 3 FSH level is an indirect indicator of if oocytes are donated from young women to older ovarian reserve. It reflects the negative feedback effects women, both embryo implantation and pregnancy rates of inhibin-B and estradiol produced by a cohort of are restored to normal levels. These results suggest that follicles at pituitary level. Most of the studies of basal the effect of age on fertility is largely a result of FSH levels are from ART cycles. The cut-off values for qualitative changes within the aging oocytes, rather basal FSH vary from 10 to 25 IU/l. The value of basal than senescent changes in the uterus. The high rates of FSH as a test for ovarian reserve in ART was evaluated pregnancy wastage in older women also indicate the in a meta-analysis of 21 studies. The results of receiver age-related decrease in oocyte quality7. Detection of operating curve (ROC) analysis have shown that the high abortion rates in oocyte donation cycles if oocytes performance of basal FSH in ART cycles to predict poor are donated from older women demonstrates that the response was moderate, where as to predict non- age-related factor responsible for pregnancy wastage is pregnancy was poor. In a systemic review, Broekmans also oocyte quality8. An increased frequency of et al10 found that the cut off FSH levels of > 10U/ L had abnormal chromosome arrangements in human oocytes a specificity of 80-90% and a lower sensitivity of 10- in older women is reported in several studies. Pre- 30% for the prediction of poor ovarian response to implantation genetic diagnosis of embryos in women gonadotropin in IVF. The lack of clear cut-off point over 38 shows high rates of aneuploidy, another with reasonable sensitivity and specificity and inter- important evidence of a strong association between cycle variations of FSH measurements also limits the advanced maternal age and pregnancy wastage9. reliability and use of basal FSH in IVF practice. The increase in basal FSH levels is a late indicator of Initial Evaluation of Ovarian Reserve: ovarian reserve. Median FSH remained consistently low (>_5 U/L) in women >_ 35 years of age and was 6 U/L in An important group of patients that has to be taken into 35 to 40 years old11. Prediction of over reserve with consideration for diminished ovarian reserve are only basal FSH may lead to an inappropriate strategy in infertile women of advanced age (>35). The proportion infertile women, and some with a diminished ovarian of older age infertile women is gradually increasing. If reserve cannot take advantage of determining the 10% of patients enter menopause before the age of 45, rapidly closing window of opportunity. Although it is then the same proportion of women are expected to known that the prognosis of ART cycles will be highly experience signs of ovarian aging in their early thirties. negative in patients with high basal FSH levels, it is Thus, it should be reasonable to test all infertile women generally accepted that the predictive value of FSH over 30 for ovarian reserve. Ovarian surgeries of any levels below cut-off values are limited to reflect the kind, but particularly for ovarian endometriosis, might outcome of ART cycles. A study evaluating the be detrimental to primordial follicle pool; thus, patients predictive value of FSH with regard to age showed that with a history of ovarian surgery need to be evaluated the ART performance of the patients over 40 but with for ovarian reserve regardless of their age. The normal basal FSH levels were worse than the patients underlying cause of subfertility might theoretically be a below 40 but with an abnormal basal FSH level.